+ Site Statistics
References:
52,654,530
Abstracts:
29,560,856
PMIDs:
28,072,755
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn

+ Translate
+ Recently Requested

Improved bioavailability of a water-insoluble drug by inhalation of drug-containing maltosyl-β-cyclodextrin microspheres using a four-fluid nozzle spray drier



Improved bioavailability of a water-insoluble drug by inhalation of drug-containing maltosyl-β-cyclodextrin microspheres using a four-fluid nozzle spray drier



Aaps Pharmscitech 13(4): 1130-1137



We previously developed a unique four-fluid nozzle spray drier that can produce water-soluble microspheres containing water-insoluble drug nanoparticles in one step without any common solvent between the water-insoluble drug and water-soluble carrier. In the present study, we focused on maltosyl-β-cyclodextrin (malt-β-CD) as a new water-soluble carrier and it was investigated whether drug/malt-β-CD microspheres could improve the bioavailability compared with our previously reported drug/mannitol (MAN) microspheres. The physicochemical properties of bare drug microparticles (ONO-2921, a model water-insoluble drug), drug/MAN microspheres, and drug/malt-β-CD microspheres were evaluated. In vitro aerosol performance, in vitro dissolution rate, and the blood concentration profiles after intratracheal administration were compared between these formulations. The mean diameter of both drug/MAN and drug/malt-β-CD microspheres was approximately 3-5 μm and both exhibited high aerosol performance (>20% in stages 2-7), but drug/malt-β-CD microspheres had superior release properties. Drug/malt-β-CD microspheres dissolved in an aqueous phase within 2 min, while drug/MAN microspheres failed to dissolve in 30 min. Inhalation of drug/malt-β-CD microspheres enhanced the area under the curve of the blood concentration curve by 15.9-fold than that of bare drug microparticles and by 6.1-fold than that of drug/MAN microspheres. Absolute bioavailability (pulmonary/intravenous route) of drug/malt-β-CD microspheres was also much higher (42%) than that of drug/MAN microspheres (6.9%). These results indicate that drug/malt-β-CD microspheres prepared by our four-fluid nozzle spray drier can improve drug solubility and pulmonary delivery.

(PDF emailed within 0-6 h: $19.90)

Accession: 036570564

Download citation: RISBibTeXText

PMID: 22945234

DOI: 10.1208/s12249-012-9826-z


Related references

Preparation of two-drug composite microparticles to improve the dissolution of insoluble drug in water for use with a 4-fluid nozzle spray drier. Journal of Controlled Release 107(3): 387-394, 2005

Improved dissolution of an insoluble drug using a 4-fluid nozzle spray-drying technique. Chemical & Pharmaceutical Bulletin 52(9): 1066-1070, 2004

One-step preparation of rifampicin/poly(lactic-co-glycolic acid) nanoparticle-containing mannitol microspheres using a four-fluid nozzle spray drier for inhalation therapy of tuberculosis. Journal of Controlled Release 135(1): 19-24, 2009

One-step preparation of drug-containing microparticles to enhance the dissolution and absorption of poorly water-soluble drugs using a 4-fluid nozzle spray drier. Journal of Controlled Release 120(3): 205-210, 2007

Preparation of drug nanoparticle-containing microparticles using a 4-fluid nozzle spray drier for oral, pulmonary, and injection dosage forms. Journal of Controlled Release 122(1): 10-15, 2007

Preparation of particles for dry powder inhalation using a novel 4-fluid nozzle spray drier. Yakuzaigaku 63(4): 228-237, November, 2003

Solubility enhancement of a poorly water-soluble anti-malarial drug: experimental design and use of a modified multifluid nozzle pilot spray drier. Journal of Pharmaceutical Sciences 98(1): 281-296, 2008

Facile synthesis of 3D cubic mesoporous silica microspheres with a controllable pore size and their application for improved delivery of a water-insoluble drug. Journal of Colloid and Interface Science 363(1): 410-417, 2011

Spray-dried nanocrystals for a highly hydrophobic drug: Increased drug loading, enhanced redispersity, and improved oral bioavailability. International Journal of Pharmaceutics 516(1-2): 372-379, 2016

Drug loading into beta-cyclodextrin granules using a supercritical fluid process for improved drug dissolution. European Journal of Pharmaceutical Sciences 33(3): 306-312, 2008

Preparation of polymeric submicron particle-containing microparticles using a 4-fluid nozzle spray drier. Pharmaceutical Research 23(1): 177-183, 2005

Pullulan-cyclodextrin microspheres. A chromatographic approach for the evaluation of the drug-cyclodextrin interactions and the determination of the drug release profiles. Journal of Chromatography B 791(1-2): 407-419, 5 July, 2003

Application of a four-fluid nozzle spray drier to prepare inhalable rifampicin-containing mannitol microparticles. Aaps Pharmscitech 9(3): 755-761, 2008

Application of a novel 3-fluid nozzle spray drying process for the microencapsulation of therapeutic agents using incompatible drug-polymer solutions. Archives of Pharmacal Research 38(4): 566-573, 2016

Effect of maltosyl-beta-cyclodextrin on drug binding to serum albumin. Yakuzaigaku 57(3): 174-180, Sept, 1997